Variant 17-49506485-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002507.4(NGFR):c.395C>T(p.Ser132Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00189 in 1,610,500 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 3 hom., cov: 31)

Exomes 𝑓: 0.0019 ( 9 hom. )

Consequence

NGFR
NM_002507.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.54

Variant links:

Genes affected

NGFR (HGNC:7809): (nerve growth factor receptor) Nerve growth factor receptor contains an extracellular domain containing four 40-amino acid repeats with 6 cysteine residues at conserved positions followed by a serine/threonine-rich region, a single transmembrane domain, and a 155-amino acid cytoplasmic domain. The cysteine-rich region contains the nerve growth factor binding domain. [provided by RefSeq, Jul 2008]

NGFR links:

NGFR-AS1 (HGNC:55555): (NGFR antisense RNA 1)

NGFR-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012102872).

BP6

Variant 17-49506485-C-T is Benign according to our data. Variant chr17-49506485-C-T is described in ClinVar as [Benign]. Clinvar id is 724414.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 307 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NGFR	NM_002507.4 link	c.395C>T	p.Ser132Leu	missense_variant	3/6	ENST00000172229.8	NP_002498.1	P08138-1
NGFR-AS1	NR_103773.1 link	n.393G>A		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NGFR	ENST00000172229.8 link	c.395C>T	p.Ser132Leu	missense_variant	3/6	1	NM_002507.4	ENSP00000172229.3	P08138-1
NGFR	ENST00000504201.1 link	c.113C>T	p.Ser38Leu	missense_variant	3/6	2		ENSP00000421731.1	P08138-2
NGFR-AS1	ENST00000514506.1 link	n.393G>A		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.00201

AC:

306

AN:

151984

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000787

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.0160

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00159

Gnomad OTH

AF:

0.000960

GnomAD3 exomes

AF:

0.00275

AC:

654

AN:

237644

Hom.:

AF XY:

0.00268

AC XY:

350

AN XY:

130550

show subpopulations

Gnomad AFR exome

AF:

0.000402

Gnomad AMR exome

AF:

0.00146

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000561

Gnomad FIN exome

AF:

0.0149

Gnomad NFE exome

AF:

0.00251

Gnomad OTH exome

AF:

0.00304

GnomAD4 exome

AF:

0.00187

AC:

2734

AN:

1458398

Hom.:

Cov.:

AF XY:

0.00178

AC XY:

1289

AN XY:

725618

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.00148

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000603

Gnomad4 FIN exome

AF:

0.0142

Gnomad4 NFE exome

AF:

0.00160

Gnomad4 OTH exome

AF:

0.00166

GnomAD4 genome

AF:

0.00202

AC:

307

AN:

152102

Hom.:

Cov.:

AF XY:

0.00269

AC XY:

200

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000786

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.0160

Gnomad4 NFE

AF:

0.00160

Gnomad4 OTH

AF:

0.000950

Alfa

AF:

0.00169

Hom.:

Bravo

AF:

0.000903

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000934

AC:

ExAC

AF:

0.00277

AC:

334

Asia WGS

AF:

0.00145

AC:

AN:

3474

EpiCase

AF:

0.00191

EpiControl

AF:

0.00160

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.50

T;.

Eigen

Benign

0.044

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.84

T;T

MetaRNN

Benign

0.012

T;T

MetaSVM

Benign

-0.49

MutationAssessor

Benign

1.4

L;.

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.2

N;N

REVEL

Uncertain

0.29

Sift

Benign

0.65

T;T

Sift4G

Benign

0.65

T;T

Polyphen

0.97

D;.

Vest4

0.32

MVP

0.83

MPC

0.67

ClinPred

0.015

GERP RS

4.4

Varity_R

0.073

gMVP

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over